Hepatobiliary Fluke Infection in Small Animals
Infection with liver flukes in endemic regions can cause acute and chronic cholangitis in cats and less frequently in dogs. The most common fluke infecting cats is Platynosomum concinnum in Florida, Hawaii, and other tropical areas. Infestation is acquired by ingesting an infected intermediate host, usually a lizard or frog; ~15%–85% of cats with access to intermediate hosts are infected in endemic areas. After infection, young flukes emerge in the intestines and migrate into the common bile duct, gallbladder, or hepatic ducts, where they mature within 8–12 wk. Embryonated eggs thereafter pass from bile into the alimentary canal, where they may be detected in feces as early as 12 wk after infection (sedimentation, Baermann test).
Clinical signs depend on severity of infection (parasite burden); however, most infested cats remain asymptomatic. Symptomatic cats demonstrate progressive illness characterized by progressive lethargy, fever, hepatomegaly, and abdominal distention. These cats may become jaundiced and emaciated secondary to anorexia, vomiting, and mucoid diarrhea. Chronic fluke infestation can be fatal in severely affected cats. First clinical signs develop between 7 and 16 wk of infection. In some cases, clinical signs resolve by 24 wk after infection without treatment. A circulating eosinophilia may develop 3–14 wk after infection and may persist. In heavily infected cats, ALT and AST activities may increase, while ALP activity may remain normal or only increase mildly. Hyperbilirubinemia may develop within 7–16 wk after infection.
Hepatic histologic lesions develop after 3 wk and are progressive in persistent infections. Inflammation and distention of large bile ducts is associated with mixed neutrophilic and eosinophilic inflammatory infiltrates. By 4 mo, severe adenomatous biliary hyperplasia and peribiliary inflammation are well established. By 6 mo, progressive fibrosis is obvious and evolves into biliary cirrhosis. Regional lymphadenopathy may be notable. Bile duct distention increases with growth of adult flukes, and when flukes become sexually mature, bile ducts become fibrotic. During this time, serum transaminase activities decline and may normalize. Abdominal ultrasonography may reveal apparent biliary obstruction involving the gallbladder, common bile duct, and/or intrahepatic ducts. Gallbladder debris associated with flukes may appear as oval hypoechoic structures having echoic centers. A thickened gallbladder wall associated with a double-rim sign may reflect cholecystitis. Hypoechoic hepatic parenchyma with prominent hyperechoic portal regions (ducts) reflects cholangitis and cholangiohepatitis.
Canine infection with Heterobilharzia americana, a schistisomal fluke, has also been characterized in dogs from Texas, North Carolina, Louisiana, and Florida. Infection is acquired through skin penetration by cercariae released from snails. These forms migrate through the host as schistosomula, reaching the lungs within 5–9 days and liver within 7–45 days. Schistosomes grow and mature in liver, with adults migrating to mesenteric veins, where they release eggs and also proteolytic enzymes upon migration to the bowel lumen. Eggs provoke a granulomatous reaction. Healing of the host leads to scar formation and organ injury that can result in liver failure and GI malabsorption.
Clinical signs of illness in dogs with schistosomiasis may manifest as early as a few days to months after infection. Young adult dogs are more commonly affected. Common clinical features (in descending order) include lethargy, weight loss, vomiting, diarrhea, inappetence, hypercalcemia, PU/PD, and more rarely, melena. The most common hematologic findings are lymphopenia and mild to marked thrombocytopenia, with eosinophilia being uncommon. Schistocytes have been seen in some dogs, reflecting intravascular shearing injury of RBCs. Common serum biochemical features include modest azotemia (BUN and creatinine), hyperglobulinemia, total and ionized hypercalcemia, and hyperglobulinemia. Liver enzyme activity is variable. Hypercalcemia is thought to reflect granulomatous inflammation. Acquired immunodeficiency (neoplasia, drug therapy) may increase susceptibility to infection.
Because fluke-infected cats may remain asymptomatic, diagnosis can be difficult. Eggs may not be detected on fecal examination, because they are only sporadically passed and demonstrate variable morphology (immature and embryonated forms). In addition, fluke eggs are small, and routinely used fecal methods are relatively insensitive for fluke egg detection. Furthermore, development of bile duct obstruction and fibrosis may impede passage of fluke eggs into bile and feces.
Suspected fluke infestation is treated with praziquantel (based on dosing extrapolated from experimentally infected animals and proved to control schistosome infection in dogs). Praziquantel at 20–25 mg/kg body wt, tid for 3 days, has been effective in some but not all treated animals. Eggs may continue to be passed in feces for up to 2 mo after successful treatment in cats, and reinfection may complicate assessment of treatment response. Some infected dogs have been treated with fenbendazole (50 mg/kg body wt/day, PO, for 10 days) with or without concurrent praziquantel administration. Prednisolone is used to reduce fluke-associated inflammation (2 mg/kg/day for 2–4 wk, tapered in 50% decrements every 2 wk). Ursodeoxycholic acid is recommended for bile duct–associated lesions given at 15–20 mg/kg, PO, divided bid and administered with food to initiate hydrocholeresis. Broad-spectrum antibiotic coverage is recommended to protect against secondary bacterial infections associated with migrating or dying flukes. Vitamin E (10 IU/kg/day, PO) and SAMe (20–40 mg/kg/day, PO) are given until liver enzymes normalize. If necessary, an antiemetic can be administered, eg, metoclopramide (0.2–0.5 mg/kg, PO or SC, every 6–8 hr) or maropitant (1 mg/kg/day for no more than 5 consecutive days).
Treatment results are variable, but prognosis is favorable in mild fluke infestation. Other rare parasites of the biliary tract include Amphimerus pseudofelineus, Metorchis conjunctus, and Eurytrema procyonis. (Also see Hepatic Flukes.) Similar assessment and treatment strategies are warranted.